title: The role of LOX and LOXL2 in scar formation after glaucoma surgery.
abstract: OBJECTIVE
  The aim of this study was to elucidate the role of lysyl oxidase (LOX) and lysyl oxidase like (LOXL) 2 in pathologic wound healing after glaucoma surgery. We therefore investigated the expression of LOX and LOXL2 and evaluated the therapeutic potential of anti-LOX (GS-639556, formerly M64) and anti-LOXL2 (GS-607601, formerly AB0023) antibodies in a rabbit model of glaucoma trabeculectomy.
  
  
  METHODS
  Ocular expression of LOX and LOXL2 was investigated by immunohistologic staining at different time points after trabeculectomy. Treatment with GS-639556 or GS-607601 was initiated in rabbits immediately after trabeculectomy by giving both intracameral and subconjunctival injections. Thereafter, the antibodies were given twice a week subconjunctivally until day 30 after surgery (day of euthanization). Treatment outcome was studied by clinical investigation of the bleb and by immunohistochemical analysis of angiogenesis, inflammation, and collagen deposition.
  
  
  RESULTS
  LOX and LOXL2 were both upregulated in Tenon's capsule and the conjunctiva after glaucoma surgery. Repeated administration of LOX- or LOXL2-targeting monoclonal antibodies increased bleb area and bleb survival. Analyses of immunohistologic stainings showed that both antibodies significantly decreased fibrosis, whereas the anti-LOXL2 antibody also significantly reduced blood vessel density and inflammation.
  
  
  CONCLUSIONS
  Targeting LOXL2 with an inhibitory monoclonal antibody (GS-607601) reduced pathologic angiogenesis, inflammation, and fibrosis. These results suggest that LOXL2 could be an appealing target for treatment of scar formation after glaucoma surgery, and point to the potential therapeutic benefits of simtuzumab, a humanized monoclonal antibody derived from GS-607601.
authors.affiliation: The Laboratory of Ophthalmology, Katholieke Universiteit Leuven, Leuven, Belgium.
authors.forename: Tine
authors.initials: T
authors.lastname: Van Bergen
authors.forename: Derek
authors.initials: D
authors.lastname: Marshall
authors.forename: Sara
authors.initials: S
authors.lastname: Van de Veire
authors.forename: Evelien
authors.initials: E
authors.lastname: Vandewalle
authors.forename: Lieve
authors.initials: L
authors.lastname: Moons
authors.forename: Jean
authors.initials: J
authors.lastname: Herman
authors.forename: Victoria
authors.initials: V
authors.lastname: Smith
authors.forename: Ingeborg
authors.initials: I
authors.lastname: Stalmans
mesh_terms: D020533:Angiogenesis Inhibitors / Q000494:pharmacology; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology; D002921:Cicatrix / Q000209:etiology / Q000378:metabolism*; D003228:Conjunctiva / Q000378:metabolism; D004195:Disease Models, Animal; D005260:Female; D005901:Glaucoma / Q000188:drug therapy / Q000378:metabolism* / Q000601:surgery; D007150:Immunohistochemistry; D011817:Rabbits; D051127:Scavenger Receptors, Class E / Q000037:antagonists & inhibitors / Q000502:physiology*; D058475:Tenon Capsule / Q000378:metabolism; D014130:Trabeculectomy
chemical_list: D020533:Angiogenesis Inhibitors; D000893:Anti-Inflammatory Agents; D051127:Scavenger Receptors, Class E
keywords: angiogenesis; fibrosis; inflammation; lysyl oxidase